ArticleAnnals of hematology2018
MYC-dependent downregulation of telomerase by FLT3 inhibitors is required for their therapeutic efficacy on acute myeloid leukemia.
Article in Annals of hematology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- WRAP53 is Downregulated in Acute Myeloid Leukemia Patients and Positively Correlates With HTERT Expression.Cancer reports (Hoboken, N.J.) · 2026Article
- Infection-Induced Telomere Length Variation: Insights into Pathogenesis of Koala Retrovirus.Viruses · 2025Article
- Development and comparison of single FLT3-inhibitors to dual FLT3/TAF1-inhibitors as an anti-leukemic approach.PloS one · 2025Article
- 8-Hydroxydaidzein Induces Apoptosis and Inhibits AML-Associated Gene Expression in U-937 Cells: Potential Phytochemical for AML Treatment.Biomolecules · 2023Article
- Dyskerin and telomerase RNA component are sex-differentially associated with outcomes and Sunitinib response in patients with clear cell renal cell carcinoma.Biology of sex differences · 2023Article
- Genomic, epigenomic, and transcriptomic signatures for telomerase complex components: a pan-cancer analysis.Molecular oncology · 2023Article
- Antiproliferative Effects of Ferulic, Coumaric, and Caffeic Acids in HepG2 Cells byAdvances in pharmacological and pharmaceutical sciences · 2022Article
- Therapeutic Targeting of FLT3 in Acute Myeloid Leukemia: Current Status and Novel Approaches.OncoTargets and therapy · 2022Review
- Review
- Thyroid Carcinoma: Phenotypic Features, Underlying Biology and Potential Relevance for Targeting Therapy.International journal of molecular sciences · 2021Review
- Telomerase reverse transcriptase promoter mutations in thyroid carcinomas: implications in precision oncology-a narrative review.Annals of translational medicine · 2020Review
- Telomere-related Markers for Cancer.Current topics in medicinal chemistry · 2020Review
- Telomerase Reverse Transcriptase (TERT) in Action: Cross-Talking with Epigenetics.International journal of molecular sciences · 2019Review
- The Myc/Max/Mxd Network Is a Target of Mutated Flt3 Signaling in Hematopoietic Stem Cells in Flt3-ITD-Induced Myeloproliferative Disease.Stem cells international · 2018Article
Corrections and comments
- Erratum issuedCorrection to: MYC-dependent downregulation of telomerase by FLT3 inhibitors is required for their therapeutic efficacy on acute myeloid leukemia.2018 · Björkhom M [corrected to Björkholm M]
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The somatic mutation of FLT3 occurs in 30% of acute myeloid leukemia (AML), with the majority of mutations exhibiting internal tandem duplication (ITD). On the other hand, the induction of telomerase reverse transcriptase (hTERT) and the activation of telomerase is a key step in AML development. Here, we sought to determine whether FLT3ITD regulates hTERT expression in AML cells and whether hTERT expression affects FLT3 inhibitors' therapeutic efficacy on AML. FLT3ITD-harboring AML cell lines and primary cells treated with the FLT3 inhibitor PKC412 displayed a rapid decline in the levels of hTERT mRNA and telomerase activity. Moreover, PKC412 inhibited hTERT gene transcription in a c-MYC-dependent manner. The ectopic expression of hTERT significantly attenuated the apoptotic effect of PKC412 on AML cells. Mechanistically, hTERT enhanced the activity of FLT3 downstream effectors or alternative RTK signaling, thereby enhancing AKT phosphorylation, in AML cells treated with PKC412. Collectively, PKC412 downregulates hTERT expression and telomerase activity in a MYC-dependent manner and this effect is required for its optimal anti-AML efficacy, while hTERT over-expression confers AML cells resistance to a targeted therapeutic agent PKC412. These findings suggest that the functional interplay between FLT3ITD and hTERT contributes to the AML pathogenesis and interferes with the efficacy of FLT3ITD-targeted therapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.